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Biomedical subjects

Matthew O'Donnell

Publications and source records attributed to Matthew O'Donnell.

At least 19 recordsLinked to original sources

Correspondence of ultrasound elasticity imaging to direct mechanical measurement in aging DVT in rats.

Previous ultrasound elasticity imaging experiments supported a generally accepted concept that the hardness of deep venous thrombi increases with thrombus aging. Results also showed that this noninvasive imaging technique can accurately predict thrombus age through strain estimates, in a well-controlled animal study. In the present study, as an alternative means to characterize elastic properties of thrombi, we used a direct mechanical measurement system to estimate Young's modulus of ex vivo thrombi. Unlike conventional indentation tests, the device uses a specific compression geometry for cylindrical tissue specimens. We also proposed an approximation scheme to retrieve Young's modulus from force-displacement measurements made using the device. Finite element simulations and calibrations on tissue-mimicking phantoms validated the system. Then, using two groups of rats with surgically-induced thrombi, we further investigated the correlation between Young's modulus measured ex vivo and elasticity images reconstructed in vivo. This comparison was accomplished by converting the intrathrombus strains measured in the in vivo studies into Young's modulus estimates using a model-based approach. Good agreement between time-dependent Young's modulus estimates observed in vivo and direct measurements of Young's modulus using the mechanical device helps to confirm the ability of elasticity imaging to age deep venous thrombi for efficient treatment.

Aging↗

Coded excitation for synthetic aperture ultrasound imaging.

Peak acoustic power limits the signal-to-noise ratio (SNR) of real-time ultrasound images. For most conventional scan formats, however, the average power is well below heating limits. This means the SNR can be significantly increased using coded excitation. A coded system transmits a broadband, temporally elongated excitation pulse with a finite time-bandwidth product. The received signal must be decoded to produce an imaging pulse with improved SNR resulting from the higher average power in the elongated excitation. Decoding can produce significant range side lobes, however, greatly reducing image quality. All practical coding designs, therefore, represent a trade-off between SNR gain and range side lobes. A specific coding scheme appropriate for synthetic aperture imaging is presented. A 14.5 dB SNR improvement with acceptable range side lobes is demonstrated on a forward-looking imaging system appropriate for intravascular applications.

Algorithms↗

Identification of vulnerable atherosclerotic plaque using IVUS-based thermal strain imaging.

Pathology and autopsy studies have demonstrated that sudden disruption of vulnerable atherosclerotic plaque is responsible for most acute coronary syndromes. These plaques are characterized by a lipid-rich core with abundant inflammatory cells and a thin fibrous cap. Thermal strain imaging (TSI) using intravascular ultrasound (IVUS) has been proposed for high-risk arterial plaque detection, in which image contrast results from the temperature dependence of sound speed. It has the potential to distinguish a lipid-laden lesion from the arterial vascular wall due to its strong contrast between water-bearing and lipid-bearing tissue. Initial simulations indicate plaque identification is possible for a 1 degrees C temperature rise. A phantom experiment using an IVUS imaging array further supports the concept, and results agree reasonably well with prediction.

Animals↗

Evaluation of ultrasound tissue damage based on changes in image echogenicity in canine kidney.

Sufficiently high intensity ultrasound can create hyperechoic regions in an ultrasound image due to local bubble generation. We explore the link between the temporal extent of these hyperechoic regions and tissue damage caused by ultrasound therapy. The decay rate of increased echogenicity from the focal zone in insonated live exteriorized canine kidney was quantified and correlated to the spatial extent of tissue damage. The decay half-time, t(half), defined as the time for echogenicity enhancement to decay by a factor of 2, was observed in all cases to be greater than 41 s in spatial zones in which extensive histological damage was observed. In cases in which the measured thalf was less than 11 s, the damage was limited to minor hemorrhage, or it was not detected. These t(half) discrimination boundaries of 41 and 11 s were not statistically different for cases in which contrast agent was used to enhance therapeutic efficiency. This was true even though contrast agent infusion significantly reduced the therapy pulse duration threshold for damage production.

Animals↗

Bubble-based acoustic radiation force elasticity imaging.

Acoustic radiation force is applied to bubbles generated by laser-induced optical breakdown (LIOB) to study viscoelastic properties of the surrounding medium. In this investigation, femtosecond laser pulses are focused in the volume of gelatin phantoms of different concentrations to form bubbles. A two-element confocal ultrasonic transducer generates acoustic radiation force on individual bubbles while monitoring their displacement within a viscoelastic medium. Tone burst pushes of varying duration have been applied by the outer element at 1.5 MHz. The inner element receives pulse-echo recordings at 7.44 MHz before, during, and after the excitation bursts, and crosscorrelation processing is performed offline to monitor bubble position. Maximum bubble displacements are inversely related to the Young's moduli for different gel phantoms, with a maximum bubble displacement of over 200 microm in a gel phantom with a Young's modulus of 1.7 kPa. Bubble displacements scale with the applied acoustic radiation force and displacements can be normalized to correct for differences in bubble size. Exponential time constants for bubble displacement curves are independent of bubble radius and follow a decreasing trend with the Young's modulus of the surrounding medium. These results demonstrate the potential for bubble-based acoustic radiation force methods to measure tissue viscoelastic properties.

Computer Simulation↗

Motion artifact reduction for IVUS-based thermal strain imaging.

Thermal strain imaging (TSI) using intravascular ultrasound (IVUS) has the potential to identify lipid pools within rupture-prone arterial plaques and serve as a valuable supplement to current IVUS systems in diagnosing acute coronary syndromes. The major challenge for in vivo application of TSI will be cardiac motion, including bulk motion and tissue deformation. Simulations based on an artery model, including a lipid-filled plaque, demonstrate that effective bulk motion compensation can be achieved within a certain motion range using spatial interpolation. We also propose a practical imaging scheme to minimize mechanical strains caused by tissue deformation based on a linear least squares fitting strategy. This scheme was tested on clinical data by artificially superimposing thermal displacements corresponding to different temperature rises. Results suggest a 1-2 degrees C temperature rise is required to detect lipids in an atherosclerotic plaque in vivo.

Arteries↗

Trapping cavitation bubbles with a self-focused laser beam.

We observed that laser-induced cavitation bubbles in water can be trapped in a self-focused laser beam. Both optical imaging and acoustic detection have been utilized to confirm bubble trapping. Transverse and longitudinal trapping forces were measured to be as large as 87 and 11 pN, respectively. This result is contrary to conventional wisdom, since the mechanism of trapping in conventional optical tweezers implies that a low-index particle (a bubble being the limiting case) should be antitrapped.

Equipment Design↗

Staging deep venous thrombosis using ultrasound elasticity imaging: animal model.

Deep venous thrombi undergo progressive hardening with age. However, the evolution rate remains poorly characterized by both invasive and noninvasive techniques. In a previous study (Emelianov et al. 2002), we demonstrated the potential of ultrasound elasticity imaging to noninvasively detect and age thrombus using a rat-based model. Knowing that thrombi harden over time is useful, but the value of the technique relies on whether the age of a thrombus can be predicted from strain estimates, and how accurate these predictions are. The objective of the present study is to answer these two questions. In the previous study, thrombus elasticity changes were monitored only on day 3, 6 and 9 after surgically induced formation of thrombosis in rat inferior vena cavas. In this study, ultrasound elasticity imaging was performed on two independent groups of rats (16 in total) starting from day 3 through day 10 with more temporal samples through the thrombus maturation process. For each rat, thrombus hardness was quantified at each scan interval by measures of normalized strains and reconstructed relative Young's moduli. In both groups, strain magnitudes exhibit progressive decrease as clots age. The relationship between the normalized strain and the clot age was developed from the first group and evaluated by the second group. Statistical analysis showed that the age estimation accuracy is within 0.8 day. If further research can successfully transfer the animal clot-hardening model to human patients, we believe that elasticity imaging will become a key component of venous compression ultrasound for effective diagnosis and treatment of deep venous thrombosis.

Animals↗

Measuring the nonlinear elastic properties of tissue-like phantoms.

A direct mechanical system simultaneously measuring external force and deformation of samples over a wide dynamic range is used to obtain force-displacement curves of tissue-like phantoms under plain strain deformation. These measurements, covering a wide deformation range, then are used to characterize the nonlinear elastic properties of the phantom materials. The model assumes incompressible media, in which several strain energy potentials are considered. Finite-element analysis is used to evaluate the performance of this material characterization procedure. The procedures developed allow calibration of nonlinear elastic phantoms for elasticity imaging experiments and finite-element simulations.

Adult↗

Finite-element analysis of material and parameter effects in laser-based thermoelastic ultrasound generation.

Laser-based, thermoelastic transduction methods have potential in very high frequency (>50 MHz), high-density two-dimensional (2-D) arrays for a variety of very high-resolution superficial imaging applications, including in vivo tissue sectioning. Previous studies of these transducers generally have been based on experimental measurements or theoretical analyses using various simplifying assumptions. These theoretical models are mostly 1-D and best matched to simple geometries with a minimum number of component materials. In this work, we use a new thermoelastic solver in a commercially available finite-element analysis (FEA) software package to analyze multidimensional effects in laser-based devices of arbitrary geometry with the potential for use with arbitrary material properties. The FEA approach was verified first against experimental data. Thereafter, we explored the impact of various design variables, including laser spot size and laser penetration depth.

Anatomy, Cross-Sectional↗

Feasibility of applying ultrasound strain imaging to detect renal transplant chronic allograft nephropathy.

Chronic renal transplantation fibrosis, often termed Chronic Allograft Nephropathy, may progress undetected. Since renal fibrosis may be accompanied by a change in measurable elastic tissue properties, ultrasound strain management may be useful in it detection. Ultrasound strain imaging was performed for two subjects with renal transplants; one with normal renal function and one with mild renal insufficiency and biopsy demonstrated fibrosis. Subjects underwent ultrasound examination with application of a controlled deformation using phase-sensitive, two-dimensional speckle tracking to evaluate internal tissue motion to measure tissue displacement and strain. Measurements over multiple beams for an equivalent deformational stress showed there was a threefold difference in renal cortical strain between the two subjects. These data suggest that ultrasound elasticity imaging may prove useful in measuring mechanical changes related to fibrosis with the transplant kidney.

Adult↗

Prospects for elasticity reconstruction in the heart.

The elastic moduli in anisotropic media can be estimated using either direct mechanical or sound speed measurements. Here we compare moduli in the passive heart estimated with different methods and demonstrate that high-frequency (i.e., ultrasonic) sound speed measurements are inconsistent with static deformations and low-frequency shear wave results. Both tissue fixation and the high-operating frequency of ultrasonic measurements contribute to these discrepancies. Moreover, the precision of ultrasonic sound speed measurements required to estimate elastic moduli describing static deformations of a nearly incompressible anisotropic medium such as the heart appears to be beyond the scope of current methods. We conclude that an incompressible anisotropic elastic model is appropriate for elasticity reconstruction in the heart, in which three independent constants characterize small strain behavior, but four are needed for a fully nonlinear description of finite deformations.

Algorithms↗

Model-based reconstructive elasticity imaging of deep venous thrombosis.

Deep venous thrombosis (DVT) and its sequela, pulmonary embolism, is a significant clinical problem. Once detected, DVT treatment is based on the age of the clot. There are no good noninvasive methods, however, to determine clot age. Previously, we demonstrated that imaging internal mechanical strains can identify and possibly age thrombus in a deep vein. In this study the deformation geometry for DVT elasticity imaging and its effect on Young's modulus estimates is addressed. A model-based reconstruction method is presented to estimate elasticity in which the clot-containing vessel is modeled as a layered cylinder. Compared to an unconstrained approach in reconstructive elasticity imaging, the proposed model-based approach has several advantages: only one component of the strain tensor is used; the minimization procedure is very fast; the method is highly efficient because an analytic solution of the forward elastic problem is used; and the method is not very sensitive to the details of the external load pattern--a characteristic that is important for free-hand, external, surface-applied deformation. The approach was tested theoretically using a numerical model, and experimentally on both tissue-like phantoms and an animal model of DVT. Results suggest that elasticity reconstruction may prove to be a practical adjunct to triplex scanning to detect, diagnose, and stage DVT.

Aging↗

Nonlinear elasticity imaging: theory and phantom study.

In tissue the Young's modulus cannot be assumed constant over a wide deformation range. For example, direct mechanical measurements on human prostate show up to a threefold increase in Young's modulus over a 10% deformation. In conventional elasticity imaging, these effects produce strain-dependent elastic contrast. Ignoring these effects generally leads to suboptimal contrast (stiffer tissues at lower strain are contrasted against softer tissues at higher strain), but measuring the nonlinear behavior results in enhanced tissue differentiation. To demonstrate the methods extracting nonlinear elastic properties, both simulations and measurements were performed on an agar-gelatin phantom. Multiple frames of phase-sensitive ultrasound data are acquired as the phantom is deformed by 12%. All interframe displacement data are brought back to the geometry of the first frame to form a three-dimensional (3-D) data set (depth, lateral, and preload dimensions). Data are fit to a 3-D second order polynomial model for each pixel that adjusts for deformation irregularities. For the phantom geometry and elastic properties considered in this paper, reconstructed frame-to-frame strain images using this model result in improved contrast to noise ratios (CNR) at all preload levels, without any sacrifice in spatial resolution. From the same model, strain hardening at all preload levels can be extracted. This is an independent contrast mechanism. Its maximum CNR occurs at 5.13% preload, and it is a 54% improvement over the best case (preload 10.6%) CNR for frame-to-frame strain reconstruction. Actual phantom measurements confirm the essential features of the simulation. Results show that modeling of the nonlinear elastic behavior has the potential to both increase detectability in elasticity imaging and provide a new independent mechanism for tissue differentiation.

Algorithms↗

Notes on synthetic phased-array with 2-D sparse arrays.

Recent advances in 3-dimensional (3-D) imaging with 2-D sparse arrays have generated renewed interest in array synthesis theory. The 3-D imaging with arbitrary planar line shapes is particularly interesting. In this correspondence, we clarify some points presented in recent publications and show that aperture synthesis can be viewed with a very simple, physical approach. Its limitations due to approximations also will be discussed.

Computer-Aided Design↗

Coded excitation with spectrum inversion (CEXSI) for ultrasound array imaging.

In this paper, a scheme called coded excitation with spectrum inversion (CEXSI) is presented. An established optimal binary code whose spectrum has no nulls and possesses the least variation is encoded as a burst for transmission. Using this optimal code, the decoding filter can be derived directly from its inverse spectrum. Various transmission techniques can be used to improve energy coupling within the system pass-band. We demonstrate its potential to achieve excellent decoding with very low (< 80 dB) side-lobes. For a 2.6 micros code, an array element with a center frequency of 10 MHz and fractional bandwidth of 38%, range side-lobes of about 40 dB have been achieved experimentally with little compromise in range resolution. The signal-to-noise ratio (SNR) improvement also has been characterized at about 14 dB. Along with simulations and experimental data, we present a formulation of the scheme, according to which CEXSI can be extended to improve SNR in sparse array imaging in general.

Algorithms↗

Thermoelastic expansion vs. piezoelectricity for high-frequency, 2-D arrays.

Optical generation using the thermoelastic effect has traditionally suffered from low conversion efficiency. We previously demonstrated increased efficiency of nearly 20 dB with an optical absorbing layer consisting of a mixture of polydimethylsiloxane (PDMS) and carbon black spin coated onto a glass microscope slide. In this paper we show that the radiated power from a black PDMS film is comparable to a 20 MHz piezoelectric two-dimensional (2-D) array element. Furthermore, we predict that a thermoelastic array element can produce similar acoustic power levels compared to ideal piezoelectric 2-D array elements at frequencies in the 100 MHz regime. We believe these results show that thermoelastic generation of ultrasound is a promising alternative to piezoelectricity for high-frequency, 2-D arrays.

Dimethylpolysiloxanes↗

A high-frequency, 2-D array element using thermoelastic expansion in PDMS.

Optical generation of ultrasound is a promising alternative to piezoelectricity for high-frequency arrays. An array element is defined by the size and location of a laser beam focused on a suitable surface. Optical generation using the thermoelastic effect has traditionally suffered from low conversion efficiency. We previously demonstrated an increase in conversion efficiency of nearly 20 dB with an optical absorbing layer consisting of a mixture of polydimethylsiloxane (PDMS) and carbon black spin coated onto a glass microscope slide. Radiation pattern measurements with an 85 MHz spherically focused transducer indicated an array element size of 20 microm. These measurements lacked the spatial resolution required to reveal fine details in the radiated acoustic field. Here we report radiation pattern measurements with a 5-microm spatial sampling, showing that the radiated acoustic field is degraded by leaky Rayleigh waves launched from the PDMS/glass interface. We demonstrate that replacing the glass with a clear PDMS substrate eliminates the leaky Rayleigh waves, producing a broad and smooth radiation pattern suitable for a two-dimensional (2-D) phased array operating at frequencies greater than 50 MHz.

Computer Simulation↗